Transplantation of stem cells capable of or having a propensity for undergoing osteogenic differentiation is a promising avenue for the treatment of bone-related diseases, especially when the treatment requires production of new bone.
Bone marrow stromal cells or mesenchymal stem cells (abbreviated as BMSC or MSC) can be readily isolated and expanded from adult bone marrow and several other tissues, based on the adherence of these cells to tissue culture plastic. MSC mostly demonstrate a tri-potential, mesoderm-related fate, i.e., the capacity to undergo osteogenic, adipocytic and chondrocytic differentiation (Pittenger et al. 1999. Science 284: 143-7), although MSC capable of producing neural, liver and muscle cells have also been reported (Prockop 1997. Science 276: 71-4).
MSC may be defined by expression of soluble and surface markers, including among others CD105, CD90 and CD73. Moreover, the prior art generally shows MSC as negative for the CD34 antigen, which is instead known to be highly expressed in immature blood and endothelial cells. In particular, CD34-positive, bone marrow originated MSC have not been described previously. Also, enhanced osteogenic and osteoregenerative properties have not been described previously for CD34-positive MSC, and particularly for CD34-positive MSC originated from bone marrow.
Bone marrow transplantation has been employed to treat bone disorders (Gangji et al. 2005. Expert Opin Biol Ther 5: 437-42). However, MSC may only represent a minor proportion of all cells present in bone marrow samples, and can moreover display variable tendencies for osteogenic differentiation, such that a considerable proportion of so-transplanted cells would not eventually contribute to the formation of the desired bone tissue. Indeed, it has been shown that only about 14% of human adult mesenchymal stem cell progenitors maintained an osteogenic potential (D'Ippolito et al. 1999. J Bone Miner Res. 14: 1115-22).
In view thereof, there exists a continuing need to improve the yield of production of osteoprogenitors, osteoblasts or bone-forming cells from mesenchymal stem cells.